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D Wallwiener

Publications and source records attributed to D Wallwiener.

At least 73 records · Page 4Linked to original sources
PubMed2001

Clinical relevance of genomic aberrations in homogeneously treated high-risk stage II/III breast cancer patients.

Little is known about the prognostic impact of chromosome aberrations in breast cancer. The aim of our study was to determine whether genomic aberrations of prognostic relevance can be identified in the context of a clinical study using molecular cytogenetics. Paraffin-embedded tumor samples of 44 patients with high-risk stage II/III breast cancer were analyzed by comparative genomic hybridization. All patients received identical therapy including dose-escalated chemotherapy followed by peripheral blood stem cell transplantation. The most frequent chromosomal aberrations were gains on chromosome arms 17q (24 cases), 1q (21 cases), 8q (17 cases), 20q (13 cases), 6p (9 cases) as well as losses on chromosome arms 13q (25 cases), 11q (20 cases), 5q (11 cases), 6q (11 cases), 9p (10 cases), 18q (10 cases), 8p (9 cases) and 16q (9 cases). In univariate analysis, the correlation with the clinical outcome revealed a higher risk for patients with tumors exhibiting 13q losses and a reduced risk for tumors exhibiting 16q losses (p = 0.020), 6q losses (p = 0.041) and estrogen-receptor positivity (0.051). In multivariate analysis using the Cox model, only the loss of 16q exhibited borderline significance (p = 0.065). These data show that comparative genomic hybridization can be performed in the context of a clinical trial. In our subgroup of high-risk breast cancer patients, chromosomal aberrations were valuable prognostic parameters.

Adult↗
PubMed2001

Effect on biochemical vasoactive markers during postmenopausal hormone replacement therapy: estradiol versus estradiol/dienogest.

OBJECTIVES: Aim was to compare the effects of estradiol-only therapy with combined estradiol/progestin treatment on the excretion of vasoactive mediators surrogating on possible effects in the vascular system. The progestin used was dienogest, a new C19-progestin with antiandrogenic properties. METHODS: Prospective, randomized trial, 25 healthy postmenopausal women treated for 3 months with estradiol valerate (2 mg/day) and 27 women with estradiol valerate (2 mg/day) continuously combined with dienogest (2 mg/day). Assessment of the following markers or their stable metabolites in nocturnal urine: cGMP, serotonin, prostacyclin and thromboxane, and urodilatin. RESULTS: Estradiol alone increased the excretion of cGMP and serotonin significantly suggesting vasodilating effects. The prostacyclin/thromboxane ratio known to be crucial for the relation of vasorelaxation to vasoconstriction significantly increased. No significant changes were found for urodilatin, which is known to elicit different effects in the cardiovascular and renal system, respectively. Combined estradiol/dienogest therapy also led to significant increases in cGMP and serotonin excretion suggesting that progestin addition for three months does not affect these markers. However, in contrast to estrogen-only treatment, there was no significant increase for the prostacyclin/thromboxane ratio, which can be explained by antagonistic action of the progestin. The excretion of urodilatin was increased significantly, which might be due to counterbalancing progestin effects in the renal vascular system. CONCLUSIONS: The changes in vasoactive markers suggest an estrogen effect that is vasorelaxant. Since there were no significant differences between the two groups, possible vascular effects of the progestin dienogest, for the first time evaluated, might not be of clinical relevance, at least not in women without cardiovascular diseases.

Administration, Oral↗
PubMed2001

A MAGE-A1 HLA-A A*0201 epitope identified by mass spectrometry.

Peptides presented by HLA-A*0201 molecules on the surface of the human breast carcinoma cell line KS24.22 after IFN-gamma induction were analyzed by the "Predict-Calibrate-Detect" approach, which combines epitope prediction and high-performance liquid chromatography mass spectrometry. One of the predicted epitopes, MAGE-A1(278-286) (KVLEYVIKV), was found to be presented by HLA-A*0201, with an estimated copy number of 18 molecules/cell. HLA-A*0201 transgenic mice (HHD mice) were used to generate CTL lines that stained positive with an HLA-A*0201 tetramer folded around the KVLEYVIKV peptide and killed peptide-loaded mouse target cells expressing HLA-A*0201. IFN-gamma-treated or -nontreated HLA-A*0201 expressing HeLa cells transiently transfected with a plasmid expressing the MAGE-A1 gene stimulated in vitro cytokine production by the CTL lines. Moreover, IFN-gamma-treated KS24.22 cells, but not IFN-gamma-treated HLA-A*0201(+) MAGE-A1(-) cells or IFN-gamma-treated HLA-A*0201(-) MAGE-A1(+) cells, were killed by these CTLS: Thus, the combination of HLA epitope prediction, peptide analysis, and immunological methods is a powerful approach for the identification of tumor-associated epitopes.

Amino Acid Sequence↗
PubMed2001

Regulated on activation, normal T-cell-expressed and -secreted mRNA expression in normal endometrium and endometriotic implants: assessment of autocrine/paracrine regulation by in situ hybridization.

Chemoattraction of macrophages and T cells into the normal endometrium and inflammatory sites within endometriotic foci is mediated by chemokine gene expression. mRNA transcripts encoding regulated on activation, normal T-cell-expressed and -secreted (RANTES), a monocyte and T-cell chemokine, were demonstrated in the stroma of normal endometrium and endometriotic implants using in situ mRNA hybridization. Epithelial glands failed to express RANTES mRNA. In histological serial sections, we observed CD68-positive macrophages in the stroma of endometriotic implants adjacent to regions with prominent RANTES mRNA hybridization. In adjacent sections, monoclonal antibodies against tumor necrosis factor (TNF)-alpha showed this cytokine to be localized to stromal and epithelial compartments of the endometriotic implant with weak staining in unaffected ovarian tissue. Subconfluent monolayers of endometriotic stromal cells were tested for RANTES gene expression in situ, but we could only detect RANTES mRNA in isolated stromal cells after treatment with TNF-alpha. No RANTES mRNA was observed in unstimulated stromal cells or TNF-alpha stimulated or unstimulated epithelial cells. The data are consistent with a model in which proinflammatory cytokines (eg, TNF-alpha) induce RANTES gene expression limited to specific cells within endometrial and endometriotic stroma. Production of this chemokine, in turn, stimulates recruitment of CD68-positive macrophages into these tissues.

Antigens, CD↗
PubMed2001

Effect of two oral contraceptives with different ethinyl estradiol and levonorgestrel concentrations on the urinary excretion of biochemical vasoactive markers.

In the present study the effect on the urinary excretion of vasoactive markers of two oral contraceptives (OCs), i.e., Leios, containing 0.02 mg ethinyl estradiol and 0.1 mg levonorgestrel, and Stediril 30, containing 0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel, was investigated. cGMP, prostacyclin and its antagonist thromboxane, serotonin, and urodilatin, a natriuretic and diuretic peptide formed in the kidney, were measured as markers. In a comparative, double-blind, randomized, parallel group study, 34 women received Leios and 33 women Stediril 30. Nocturnal urine was collected before treatment and during cyclic treatment after 3 and 12 cycles. Both contraceptives significantly enhanced cGMP excretion after 12 cycles. The prostacyclin metabolite remained unchanged for both formulations, but the excretion of the thromboxane metabolite was significantly decreased after 12 cycles. Thus, the ratio of prostacyclin to thromboxane, crucial for the resulting effect on vascular tone, increased significantly. For the serotonin metabolite, no changes were observed for both contraceptives. The excretion of urodilatin significantly increased for both preparations after 12 cycles compared to the pretreatment values. These results indicate that the low-dose OCs Leios and Stediril 30 may stimulate the production of some vasoactive markers, at least after 12 cycles of treatment. The positive influence of these contraceptives on the various markers investigated may improve vascular tone, impede development of atherosclerosis and arterial thrombosis, and improve water and electrolyte homeostasis. These effects most likely can be attributed to the estrogenic component. Levonorgestrel may elicit no impact on these estrogen-induced changes that, however, seem only to be manifested after a longer treatment period.

Adult↗
PubMed2001

[Can follow-up controls improve the accuracy of MR mammography? A retrospective analysis of MR mammography follow-up studies].

PURPOSE: To assess the change in diagnostic confidence between first and follow-up dynamic MR examination of the breast (MRM). METHODS: The reports of a total of 175 MRM in 77 patients (mean age 50 years; 36-76) with 98 follow-up MRM were analyzed. All examinations were performed as a dynamic study (Gd-DTPA, 0.16 mmol/kg; 6-7 repetitive studies). The change in diagnostic confidence was retrospectively classified as follows: controlled lesion vanished during follow-up (category I); diagnostic confidence increases during follow-up (II), more likely benign (IIa), more suspicious (IIb); no difference in diagnostic confidence (III). Long-term follow-up over an average of four years was obtained for 57 patients with category IIa/III findings. RESULTS: In 98 follow-up examinations, only two lesions vanished (2%). In 77/98 cases a category IIa lesion was diagnosed, in 11 cases a category IIb lesion. In 8 cases (8%) there was no change in diagnostic confidence during follow-up. Lesions in category IIb underwent biopsy in 10/11 cases, in one case long-term follow-up proved a completely regredient inflammatory change. In 8/11 suspicious findings (IIb) a malignant tumor was detected. The mean time interval between first and follow-up MRM was 8 months for I-IIb lesions, and 4 months for category III lesions. In the long-term follow-up two patients with a category IIa lesion developed a carcinoma in a different breast area after four and five years. CONCLUSION: MRM follow up increases the diagnostic confidence if the time interval is adequate (> 4 months). A persistently or increasingly suspicious finding warrants biopsy.

Adult↗
PubMed2001

[Clinical experience with large-core needle biopsies of the breast and evaluation of histopathology].

OBJECTIVE: Interventional techniques allow a microinvasive diagnostic of breast lesions. We examined the reliability of large core needle biopsies for histologic diagnosis on breast lesions. MATERIAL AND METHODS: 143 ultrasound guided automated spring gun biopsies and 16 stereotactic guided vacuum-assisted device biopsies were analyzed. Indications included confirmation of malign or benign lesions and diagnosis of suspicious lesions. RESULTS: In 113 biopsies (71%) an invasive breast carcinoma was diagnosed, in 5 biopsies (3%) in situ/atypical lesions were seen and 38 cases (24%) showed benign lesions. Based on the bioptic results, 108 patients underwent subsequent surgery. An identical histology was seen in 100/108 patients (93%), 5 biopsies were false negative (5%) and 3 specimens yielded necrotic/insufficient material. The immunohistochemical results of percutaneous biopsies and surgical specimens were comparable. 17 out of 113 patients (15%) with biopsy proven carcinoma were treated with neoadjuvant therapy. 32/38 patients with benign lesions were follow-up clinically. CONCLUSION: Ultrasound- or stereotactic guided percutaneous biopsies are methods to confirm histological diagnosis. Based on the biopsy results the, number of surgical excisions can be reduced and treatment of biopsy proven carcinoma can be improved by individual presurgical planing.

Biomarkers, Tumor↗
PubMed2001

Further evidence for direct vascular actions of statins: effect on endothelial nitric oxide synthase and adhesion molecules.

The effect of the synthetic statin fluvastatin was investigated on the concentrations of endothelial nitric oxide synthase (eNOS) and of soluble adhesion molecules in human vascular endothelial cell cultures. Fluvastatin was able to increase dose-dependently eNOS concentration. In addition, fluvastatin reduced concentrations of E-Selectin and ICAM-1. These results further support the evidence that statins elicit important effects on the vascular endothelium which may contribute to the reduction of morbidity and mortality of cardiovascular diseases.

Cells, Cultured↗
PubMed2001

Regulation of estrogen receptor alpha and progesterone receptor (isoform A and B) expression in cultured human endometrial cells.

The effects of RU 486 together with estradiol and progesterone on estrogen receptor alpha and progesterone receptor (isoforms A and B) expression were studied in human endometrial long term cultures at the mRNA and protein level. We asked whether ligand induced receptor regulation, found in mammals in vivo, is also found in human cultured endometrial cells with special regard to the progesterone isoforms A and B. Endometrial cultures were maintained for 27 days. Media were supplemented with progesterone and/or estradiol alone or in combination with RU 486. Receptor expression (estrogen receptor alpha and progesterone receptor isoform A and B) was examined at the mRNA level by RT-PCR and at the protein level by western blot analysis. All receptor types examined were expressed in our culture model. Estradiol led to a general increase of receptor expression whereas treatment with estradiol in combination with progesterone down regulated receptor expression. The receptor down regulation was not found when RU 486 was additionally supplemented into the medium. Activation or inhibition of expression due to these treatments was similar for both PR isoforms. Our results (1) show that in our culture system estradiol induced up regulation of estrogen receptor and progesterone receptor A and B and suggest that the estrogen induced up regulation is prevented by progesterone (2) a clear cut antigestagenic effect of RU 486 and (3) suggest that both progesterone isoforms are analogously regulated in our culture model. We conclude that human endometrial cell cultures are suitable for the study of the dynamics of steroid receptor expression.

Blotting, Western↗
PubMed2001

[Effect of tibolone on vascular markers of human female coronary arteries - comparison with estradiol/norethisterone].

OBJECTIVES: Tibolone, a synthetic norethynodrel derivative, is effective at alleviating climacteric complaints and for osteoporosis prophylaxis. Concerning the cardiovascular system little data are available on possible direct effects on the vasculature compared with hormone replacement therapy. Since tibolone is pharmacologically best comparable to an estradiol/norethisterone combination (E2/NET), the aim of the present study was to compare these treatment regimens with respect to their effects on human vascular cells, this being the first study to investigate this question. - MATERIAL AND METHODS: Human female coronary arteries were used, the most appropriate vessels for our issue in question. The experiments were conducted with endothelial cells as well as smooth muscle cells. Tibolone and E2/NET were tested at the concentrations 0.1, 1 und 10 microM. Incubation time was 24 h for endothelial cell cultures and 7 days for smooth muscle cell cultures. The effects on markers of pathophysiologically different problems were studied in a comparable manner: Markers of endothelial function such as prostacyclin, endothelin and plasminogen-activator-inhibitor-1 (PAI-1), markers of plaque initiation such as the adhesion molecules E-Selectin, ICAM-1 and the monocyte attraction protein-1 (MCP-1) and markers of plaque stability such as the precursor of the matrix-metalloproteinase-1 (pro-MMP-1). - RESULTS: Tibolone reduced the synthesis of endothelin as well as the concentrations of E-Selectin, PAI-1 and pro-MMP-1. The magnitude of the effects on these markers varied and was in the range of 11-42 %. similar inhibitions were seen for E2/NET; yet a significantly stronger inhibitory effect was found for pro-MMP-1. Moreover, E2/NET also reduced concentrations of ICAM-1 and MCP-1. Concerning smooth muscle cells only E2/NET was able to elicit an anti-proliferative effect. - CONCLUSIONS: Tibolone can positively influence the synthesis of markers in cell cultures of human female coronary artery which modulate vascular tone and which play a decisive role in the various stages of atherosclerosis. In this respect estradiol combined with norethisterone is as potent as tibolone, in addition this combination is partially more effective and able to influence a wider range of markers which are important in the early stages of atherogenesis or for the stability of atherosclerotic plaques. Experimental studies such as the present one are useful to explore mechanisms, but clearly cannot replace clinical studies.

Cell Division↗
PubMed2001

Technical results of falloposcopy for infertility diagnosis in a large multicentre study.

Despite increasing evidence of its potential clinical value, falloposcopy has not yet found widespread use. In a large prospective international multicentre study we investigated the hypothesis that limited technical reproducibility may be of crucial significance in this regard. From 1994 to 1998, data on 367 patients with 639 tubes were recorded from 18 centres (median number of falloposcopies 22). Falloposcopy was performed using hysteroscopic ostium access, coaxial tubal cannulation and retrograde visualization under laparoscopic control. The procedure was successful in 69.6% of the tubes. Failures occurred in 6.1% during hysteroscopy, in 10.6% during the cannulation step and in 16.4% during visualization. While predominantly intracavitary pathology or thick endometrium were found to interfere with hysteroscopic ostium access, technical insufficiencies resulting in catheter damage or vision disturbing light reflexions were identified to be responsible for most cannulation and visualization failures, confirming the importance of these factors. The number of patients who received a complete falloposcopic evaluation did not exceed 57%. Additionally, 23.7% of patients may have profited from unilateral success depending on the individual indication. As a consequence of these technically limited results it was concluded that the method currently qualifies for selected indications rather than for routine clinical application.

Adolescent↗
PubMed2001

Chemokine bioactivity of RANTES in endometriotic and normal endometrial stromal cells and peritoneal fluid.

Endometriotic lesions secrete chemokines that recruit immune cells into the peritoneal cavity. The accumulation of these immune cells, especially activated macrophages and T lymphocytes, is thought to mediate inflammatory symptoms associated with endometriosis. Previous studies have demonstrated that RANTES (regulated on activation, normal T cell expressed and secreted) is synthesized by endometriotic stromal cells and circulates in peritoneal fluid, commensurate with the stage of endometriosis. In the current studies, we used the human monocytic cell line, U937, to assay chemotactic activity in cell culture conditioned media and peritoneal fluid from patients with endometriosis and normal controls. We demonstrated expression of the human RANTES receptors CCR-1 and CCR-5 in U937 cells and peritoneal macrophages. Over a range of 0-1000 pg/ml recombinant human RANTES had a direct, linear effect on monocyte migration. Conditioned media and peritoneal fluid induced dose-dependent effects on monocyte migration that were correlated with concentrations of immunoreactive RANTES (as measured by enzyme-linked immunosorbent assay) and the severity of endometriosis. Heat denaturation of the RANTES protein or addition of anti-human RANTES antibodies neutralized the chemoattractant effects of conditioned media and peritoneal fluid. RANTES stimulation of monocyte recruitment may be an important pathogenetic target for the treatment of infertility and pain associated with endometriosis.

Ascitic Fluid↗
PubMed2001

Nuclear peroxisome proliferator-activated receptors alpha and gamma have opposing effects on monocyte chemotaxis in endometriosis.

The peroxisome proliferator-activated receptors (PPARs) alpha and gamma are nuclear receptors that play important roles in inflammatory diseases like ulcerative colitis and arthritis. In this study, we examined the possible role of PPARs in macrophage attraction into the peritoneal cavity of patients with endometriosis. We identified PPAR-alpha and -gamma messenger RNA by RT-PCR and protein by immunoblotting of lysates of peritoneal macrophages and monocytic U937 cells. Using immunocytochemistry, we localized PPAR-alpha and -gamma within the nuclei of both cell types. Monocyte chemotactic activity of peritoneal fluid from patients with endometriosis was quantified in Boyden chambers. Migration of U937 cells was increased by WY 14643 and reduced by rosiglitazone. Peritoneal fluid from patients with endometriosis activated U937 cells transiently transfected with a PPAR-alpha/GAL4 luciferase reporter. By contrast, peritoneal fluid did not cause significant activation of PPAR-gamma/GAL4 constructs. The U937 cells transiently transfected with a PPAR response element luciferase reporter showed disease stage-dependent up-regulation when treated with peritoneal fluid from patients with endometriosis. Treatment with peritoneal fluid from healthy controls down-regulated PPAR response element transactivation. We conclude that peritoneal fluid of endometriosis patients contains activators of PPAR-alpha that stimulate macrophage chemotaxis. Inhibitors of PPAR-alpha or activators of PPAR-gamma could be developed for the treatment of inflammation associated with endometriosis.

Apoptosis↗
PubMed2001

Valsartan and candesartan can inhibit deteriorating effects of angiotensin II on coronary endothelial function.

The angiotensin II (Ang II) AT1-receptor antagonists, valsartan and candesartan, were compared with regard to their effect on Ang II-mediated changes in parameters of coronary endothelial function. Ang II (10 microM) induced increased concentrations of the vasoconstrictor endothelin, the procoagulatory substance plasminogen-activator-inhibitor-1 (PAI-1) and the precursor of the matrix-metalloproteinase 1 (MMP-1) in endothelial cell cultures from human coronary arteries. These increases were completely prevented by the addition of 10 microM valsartan or candesartan and partially by the addition of lower concentrations of these drugs, i.e. 1 microM and 0.1 microM. No significant difference between the effect of the two AT1-receptor antagonists was observed. These results suggest that AT1-receptor antagonists not only can reduce blood pressure by blocking the action of Ang II, but might also contribute to the prevention of atherogenesis and plaque instability.

Angiotensin II↗
PubMed2001

Immunological consolidation of ovarian carcinoma recurrences with monoclonal anti-idiotype antibody ACA125: immune responses and survival in palliative treatment. See The biology behind: K. A. Foon and M. Bhattacharya-Chatterjee, Are solid tumor anti-idiotype vaccines ready for prime time? Clin. Cancer Res., 7:1112-1115, 2001.

The aim of the present study was to assess whether the induction of specific immune responses by vaccination with the murine monoclonal anti-idiotypic antibody ACA125, which imitates the tumor-associated antigen CA125, has a positive influence on the survival of patients with recurrent ovarian carcinoma. Forty-two patients with platinum-pretreated recurrences were included in a clinical Phase I/II trial of consolidation in third-line therapy. Patients initially received four immunizations with 2 mg of alum-precipitated anti-idiotype ACA125 every 2 weeks and then monthly applications. No serious allergic reactions could be detected within a maximal control period of 56 months. Hyperimmune sera of 27 of 42 patients (64.2%) showed increased concentrations of human antimouse antibodies. Specific anti-anti-idiotypic antibodies as a marker for induced immunity were detected in 28 of 42 patients (66.7%). The survival of the whole ACA125-treated collective of patients after a mean of 12.6 antibody applications was 14.9 +/- 12.9 months. The survival of patients with a positive immune response was 19.9 +/- 13.1 months in contrast with 5.3 +/- 4.3 months in those patients without detectable anti-CA125 immunity (P < 0.0001). According to these results, vaccination with a suitable anti-idiotypic antibody offers an effective way to induce specific immunity against a primarily nonimmunogenic tumor antigen such as CA125 and is associated with a positive impact on the survival of patients with recurrent ovarian cancer with few side effects, which warrants a Phase III trial for ovarian cancer patients after primary therapy.

Antibodies, Anti-Idiotypic↗
PubMed2001

Lipid-independent effects of an estrogen-statin combination: inhibition of expression of adhesion molecules and plasminogen activator inhibitor--I in human endothelial cell cultures.

OBJECTIVE: Estrogens have been shown to elicit beneficial effects on the cardiovascular system by modulating the lipid profile as well as by direct vascular actions. Since estrogenic cardioprotection has still been not confirmed by randomized interventional trials, the combination with statins, which have been proved to act in a cardioprotective fashion, is of special interest. Statins are lipid-lowering drugs, but direct vascular effects also seem to be of importance in this case. Apart from some clinical studies investigating the effect of such combination therapy on the lipid profile, no reports of a possible influence on biochemical markers of vascular function are yet available. The aim of the present study was to investigate, for the first time, lipid-independent effects of an estrogen-statin combination on markers of vascular endothelial function. METHODS: Experiments were conducted using endothelial cell cultures from human umbilical veins. Markers of endothelial function chosen were adhesion molecules, which are involved in the early stages of atherosclerosis, and plasminogen activator inhibitor-1 (PAI-1), which is an independent risk factor for the development of cardiovascular disease. The concentrations of soluble forms of the adhesion molecules E-selectin and intercellular adhesion molecule (ICAM) as well as concentrations of PAI-1 were measured after the addition of 17 beta-estradiol, fluvastatin and equimolar combinations of the two in concentrations of 0.01, 0.1 and 1 mumol/l. RESULTS: Both drugs significantly reduced concentrations of E-selectin and ICAM, and the effect of the combination was not superior to that of the monosubstances. In addition, both substances were able to inhibit the synthesis of PAI-1. In this case the effect of the combination was significantly greater than that of the monosubstances. CONCLUSION: In summary, an estrogen-statin therapy is able to elicit lipid-independent positive modulations on the expression of cell adhesion molecules and the synthesis of PAI-1. The estrogen-statin combination showed partially additive effects and no negative, antagonistic actions. Since the combination of statins with hormone replacement therapy may attain clinical significance in preventing cardiovascular disease, it seems worthwhile to elucidate further the direct vascular effects of this combination therapy, especially in postmenopausal women with pre-existing coronary disease.

Anticholesteremic Agents↗
PubMed2001

The effect of medroxyprogesterone acetate and norethisterone on the estradiol stimulated proliferation in MCF-7 cells: comparison of continuous combined versus sequential combined estradiol/progestin treatment.

OBJECTIVE: Little is known on the type of progestin and regimen type in relation to breast cancer risk. We have compared the effect of medroxyprogesterone acetate (MPA) and norethisterone (NET) on the estradiol stimulated proliferation in MCF-7 cells with respect to different regimens used in combined hormone replacement therapy (HRT). DESIGN: To approximate the in vivo conditions in HRT, MCF-7 cultures were pretreated with estradiol followed by estradiol/progestin treatment to represent the sequential combined model and compared with non pretreated cultures followed by estradiol/progestin treatment for the continuous combined model. RESULTS: When using progestins in the continuous combined form with estradiol (10(-10) M) both progestins showed a significant reduction in the estradiol stimulated proliferation of the MCF-7 cells. In the sequential combined model the addition of MPA led to a stronger significant reduction of MCF-7 proliferation but in a narrower concentration range (from 10(-8) to 10(-6) M) compared to the continuous treatment. NET did not show any significant effect on proliferation in the SC model. CONCLUSION: Different regimen types and different progestins do lead to significantly different effects on the proliferation of a breast cancer cell line. These findings might be useful in the elucidation of potential mechanisms involved in the clinical situation.

Antineoplastic Agents, Hormonal↗